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Clinical Manifestations.

Ramit Ravona-Springer1,2,3, Shiraz Vered4, Abigail Livny3,5,6,7

  • 1Geriatric psychiatry and memory unit, Sheba Medical Center, Ramat Gan, Israel.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Reduced white matter integrity in specific brain areas is linked to more depressive symptoms in middle-aged individuals at high risk for Alzheimer's disease and related disorders (ADRD). This suggests white matter changes may be early neurodegeneration markers.

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Area of Science:

  • Neuroimaging
  • Neurodegenerative Diseases
  • Mental Health

Background:

  • Reduced white-matter integrity may precede other brain imaging findings in individuals at risk for Alzheimer's disease and related disorders (ADRD).
  • This integrity loss could be involved in the development and consequences of depression.
  • Investigating this link in high-risk middle-aged individuals may reveal early neurodegeneration markers.

Purpose of the Study:

  • To examine the relationship between white matter integrity and depressive symptoms.
  • To identify potential early markers of neurodegeneration in individuals at high risk for ADRD.

Main Methods:

  • Diffusion tensor imaging (DTI) assessed white matter integrity (fractional anisotropy and mean diffusivity).
  • The Center for Epidemiological Studies-Depression (CESD) scale measured depressive symptoms.
  • Linear and logistic regression models analyzed associations in 301 cognitively normal offspring of ADRD patients.

Main Results:

  • Higher fractional anisotropy (FA) in the genu and cingulum was associated with lower CESD scores.
  • Increased FA in these areas also correlated with decreased odds of clinical depression.
  • No significant associations were found between other white matter tracts or mean diffusivity (MD) and depressive symptoms.

Conclusions:

  • Disrupted white matter integrity in specific tracts is linked to depressive symptoms in midlife individuals at increased ADRD risk.
  • These white matter alterations may serve as early biomarkers for neurodegeneration.
  • Findings suggest potential for timely intervention and prevention strategies targeting white matter health.